Infant formula with improved protein content

Description of the invention

The present invention relates to an infant formula and a method of producing a protein hydrolyzate.

In infants, especially infants up to 6 months of age, the digestive system must develop and adapt to food. For this reason, for the first months of their lives, infants are usually fed specialized infant formulas.

Such infant formula is usually well tolerated. However, in some cases, traditional milk mixtures can lead to minor problems, in particular related to the processes taking place in the gastrointestinal tract.

More specifically, it has been found in the studies leading to the present invention that conventional milk formulas can lead to undesirable disturbances of the natural intestinal flora and / or to the development of unnatural intestinal flora. It has also been found that conventional infant formulas may deliver the wrong type of substance and / or the wrong amount of substance; and / or they may have the wrong nutritional composition.

Such deficiencies in traditional milk formulas can lead to undesirable processes in the gastrointestinal tract and / or to undesirable disturbances of natural processes. This, in turn, can lead to symptoms such as:

- undesirable stool composition (for example diarrhea, constipation or an unusual color shade);

high local gas production which may cause cramps in the infant's intestines and / or gas and delayed gastric emptying;

- reduced bioavailability of divalent cations;

- undesirable levels of aggressive factors in the stool, especially factors that can irritate and / or damage epithelial cells (such as those that line the gastrointestinal tract and / or the skin), including but not limited to proteases.

As a result, infants who are fed with traditional formula formulas may suffer from reduced appetite and / or regurgitation (common in intestinal disorders). There may also be disturbances in the natural processes of gastric emptying, and an irregular pattern of food consumption may develop which may result in hunger, resulting in infants consuming large volumes of formula too quickly, which may lead to excessive glaucoma (aerophagy) and / or regurgitation. get food.

As a result of the above problems, adverse events and factors, this infant fed with traditional formulas may also suffer from impaired immune function, which can be seen in the rapid development of a rash on the buttock skin; due to malnutrition (growth failure), malfunctions (colic) or even damage to the intestine (nutrient intolerance).

Thus, there is a need for an infant formula that has improved characteristics with respect to the prevention and / or alleviation of one or more, preferably all, of the above-mentioned problems. The present invention provides such an infant formula.

In this regard, it is also particularly important that the milk formula according to the invention is capable of preventing, alleviating and / or reducing all of the above-mentioned problems simultaneously. This is because it can be extremely difficult for parents, in particular, to determine the cause of the problem (s). Thus, by using an infant formula according to the invention that can prevent and / or alleviate all of the above-mentioned problems at the same time, parents can rest assured that by using this particular formula, all such problems can be reduced, whatever their cause. and without having to switch from one formula to another until one turns out to be the right formula for babies, which alleviates the problem (s) present at the moment without causing any of the other problems mentioned above.

Usually, when one or more of these problems arise or persist, parents will begin changing formula formulas or, if that doesn't help, consult your pediatrician. However, despite the presence of such a large number of infant formulas on the market, none of them have characteristics that could prevent or alleviate all of the above-mentioned problems at the same time. Thus, switching from one formula to another may not alleviate the current problem and / or may lead to one or more further problems.

From among those mentioned above. Also, the baby may have trouble getting used to (the taste of) the new formula, which can lead to a reduction in his appetite. This, in turn, can be a particular problem when, due to the above-mentioned problems, the milk formula is or needs to be changed several times.

In the studies leading to the present invention, it has been found that some of the main causes of disturbances in the gastrointestinal processes that may arise with the use of traditional infant formulas include:

the fact that in the triglycerides present in the (lipid component) of traditional infant formulas, usually at the Sn1 position or the Sn3 position of the glycerol, undesirably high amounts of palmitic acid, myristic acid and / or stearic acid are present;

- the fact that traditional infant formulas usually contain undesirably high amounts of divalent cations, and particularly undesirable high amounts of calcium ions. This is a particular problem when high amounts of palmitic acid, myristic acid and / or stearic acid, such as those mentioned above, are present at the Sn1 position or the Sn3 position of the triglycerides at the same time;

- the fact that traditional infant formulas contain insufficient amounts of substrates beneficial for the development of microorganisms, i.e. for the naturally occurring intestinal flora.

Thus, according to the invention, all the above-mentioned problems are solved by the following measures, resulting in the infant formula.

The subject of the invention is a formula for infants containing at least one protein component with a phosphorus content lower than 0.75 g P / 100 g of protein, characterized in that it contains:

a) from 6.4 to 16% by weight of at least one protein component,

b) from 18 to 29% by weight of at least one lipid component which can be easily digested by the infant, containing fatty acid triglyceride, in which palmitic acid residues constitute more than 10% up to 30% of all fatty acid residues present in the triglyceride, and

c) from 3 to 15% by weight of at least one prebiotic component selected from the group consisting of lacto-N-tetraose, lacto-N-fucopentaose, lactulose, lactosaccharose, raffinose, galacto-oligosaccharides, fructo-oligosaccharides, oligosaccharides derived from polysaccharides, polysaccharides based on mannose, arabinoligosaccharides, xylo-oligosaccharides, isomalto-oligosaccharides, glucans, sialyl oligosaccharides and fuco-oligosaccharides, where% by weight is based on the total weight of the final dairy formula.

Preferably the milk formula comprises a protein component a) which has a phosphorus content of less than 0.72 g P / 100 g of protein, more preferably less than 0.69 g of P / 100 g of protein.

Preferably, the lipid component b) comprises triglycerides in which the palmitic acid residues at the Sn1 or Sn3 position constitute no more than 16% of the total triglycerides present.

Preferably the mixture comprises at least one protein component a) which is a hydrolyzate obtained by hydrolysis of a starting material containing proteins from mammalian milk or a dephosphated protein of vegetable origin in combination with at least one endo- and at least one exoproteinase.

Preferably, the mixture as protein component a) comprises a hydrolyzate obtained by hydrolyzing a starting material containing milk protein, a milk protein mixture and / or a milk protein preparation in combination with at least one endo- and at least one exoproteinase.

Preferably, at least one TOS trans-galacto-oligosaccharide, at least one FOS fructo-oligosaccharide and / or mixtures thereof are used as prebiotic components, in particular mixtures of at least one trans-galacto-oligosaccharide and at least one fructo-oligosaccharide, wherein the ratio of TOS to FOS is in the range of 5: 1 to 15: 1.

Preferably the mixture contains free amino acids derived from the protein hydrolyzate a) in an amount of less than 10 g and preferably in an amount of less than 7 g per 100 g of protein equivalent.

Preferably the osmolarity of the blend is less than 270 mOsmol / L, preferably less than 240 mOsmol / L.

Preferably the formula contains less than 80 mg / 418.7 kJ (100 kcal) expressed as mg calcium per 418.7 kJ (100 kcal) energy contained in the formula) and is intended for infants below the age of 6 months.

PL 199 368 B1

Preferably the formula contains less than 122 mg / 418.7 kcal (100 kcal) expressed as mg calcium per 418.7 kJ (100 kcal) energy contained in the formula and is intended for infants under the age of 6 months.

Preferably the blend comprises calcium and phosphorus with a calcium to phosphorus ratio in the range of 1.4 to 2.

Preferably, the total fat content expressed as total lipid content is in the range of 20 to 45 wt.%.

Preferably the blend comprises an additional viscosity improving component d) in an amount of from 1.5 to 15% by weight.

Preferably the viscosity of the blend is in the range from 20 to 100 mPas, preferably from 40 to 80 mPas, when measured with a Brookfield viscometer at 30 rpm.

Preferably the formula contains lactose in an amount of at most 6.0 g / 100 ml, preferably at most 4.5 g / 100 ml of the total formula formula.

The invention also relates to a process for the preparation of a protein hydrolyzate as defined above, wherein at least 50% by weight of the proteins present in the hydrolyzate, based on all protein components present in the mixture including free amino acids, have a chain length in the range of 2 to 30 amino acids and the free amino acid content is low and is less than 10% by weight, characterized by the hydrolysis of the protein starting material containing the milk protein, a mixture of milk proteins and / or a milk protein preparation with a phosphorus content of less than 0.75 g P / 100 g protein, in combination with at least one endo- and at least one exoproteinase, whereby a mixture containing enzymes: alcalase and flavourzyme proteases, and trypsin.

Preferably, proteins are hydrolyzed from mammalian milk, especially cow's milk, such as whey, especially acid whey; dephosphated casein; or a suitable mixture thereof.

Preferably the starting material is used which further comprises a yeast cell suspension in an amount of 1 to 8 g dry yeast cell weight per 100 g protein.

Preferably, the hydrolysis is carried out at a temperature of 45 to 60 ° C, the hydrolysis being completed by cooling the entire reaction mixture from the hydrolysis temperature to a temperature of less than 20 ° C, preferably less than 10 ° C, for a period of 10 minutes to 1 hour. .

The infant formula according to the invention - in its lipid / triglyceride components - does not contain large amounts of the aforementioned saturated acids neither at the Sn1 position nor at the Sn3 position of glycerol, and in particular it does not contain large amounts of palmitic acid either at the Sn1 position or the Sn3 position. This can be achieved by using a lipid component in the preparation of the infant formula according to the invention which:

- contains lipids with relatively large amounts of C14: 0, C16: 0 and C18: 0 fatty acids in the Sn2 position of glycerol, such as specific phospholipids or triglycerides of animal, microbiological or plant origin in which the triglycerides have been enzymatically or otherwise reesterified such that a high percentage of palmitic acid residues are present at position 2;

- it contains relatively small amounts of C14: 0, C16: 0 and C18: 0 fatty acids, especially C16: 0.

The infant formula according to the invention contains relatively small amounts of divalent cations, especially magnesium and / or calcium, preferably it contains particularly small amounts of calcium ions, i.e. the amounts indicated below.

In combination with, in addition to (or even in place of) these small amounts of calcium, the bioavailability of these cations according to the invention can be significantly improved; for example by ensuring that at a pH of 6-7 (i.e. under duodenal conditions), most of the calcium salts provided by the formula formula are water-soluble salts (e.g., no or only low levels of basic phosphate salts and / or basic citrate salts).

Also preferably, as already mentioned above, the amount of phosphorus in the infant formula should be as low as possible, for example as defined below. In other words, according to the invention, this can be achieved by using proteins, in particular protein hydrolysates, with a low phosphorus content, as described hereinafter.

The use of a protein hydrolyzate therefore also ensures that the protein components present in the infant formula of the invention do not sensitize the infants. The use of the hydrolysates also ensures that the protein components can be easily absorbed from the gastrointestinal tract and therefore do not interfere (excessively) with the processes taking place in the intestines (especially in the colon).

Also, as described below, the use of a protein hydrolyzate - in combination with the beneficial osmotic value provided by the formula milk of the invention - will promote natural gastric emptying processes which will prevent and / or reduce food regurgitation.

The infant formula of the invention contains a sufficient amount of substrate for the development and maintenance of a beneficial flora throughout the intestine, especially in the colon. This ensures the uniform production of gases and beneficial substances, such as short chain fatty acids, and also prevents the release of excessive amounts of aggressive agents. In human milk, the supply of such substrates is ensured by lactose and oligosaccharides. However, in traditional milk mixtures, lactose is unfortunately the only source. It has been found that the most preferred source of oligosaccharides is in the general purpose formula of the invention, for example in addition to or in place of lactose, the second variant (instead of) being particularly recommended for those infants who are (partially) lactose intolerant.

Thus, the invention provides an infant formula that comprises any combination of two or more, preferably three or more, and most preferably all of the following ingredients:

a) at least one protein component (referred to herein as "component A);

b) at least one lipid component which can be easily digested by an infant ("component B);

c) at least one prebiotic component ("component C);

d) at least one viscosity enhancing ingredient ("component D) and which optionally also includes any known formula ingredient as such, including but not limited to the ingredients described below (referred to herein as" further ingredients), and the components A to D and further components of which are preferably those described below.

The protein component may contain whole proteins and / or a protein hydrolyzate, or a mixture thereof, and most preferably has a low phosphorus content, preferably the phosphorus content is less than 0.75 g / 100 g protein. Where the protein component comprises whole proteins, it is also most preferably those that are easily digested by the infant, for example as described below.

As the source of the protein component, mammalian milk is preferably used, for example cow, goat or mare's milk.

In a particular case, the infant formula according to the invention is characterized in that the protein component a) is a protein hydrolyzate obtained by hydrolysis of a starting material containing milk protein, a milk protein mixture, and / or a milk protein preparation in combination with at least one endogen. - and at least one exoproteinase, and is further characterized by that at least one lipid component b) comprises at least one fatty acid triglyceride and / or a mixture of fatty acid triglycerides wherein:

- palmitic acid residues represent more than 10%, for example up to 30% or more, preferably 16-24%, of all fatty acid residues present in these triglycerides; and in which:

- triglycerides in which the palmitate residues are at the Sn1 position or the Sn3 position constitute no more than 16%, more preferably no more than 13% and most preferably no more than 10.7% of the total triglycerides present.

Most preferably the infant formula according to the invention - that is to say containing any two or more, preferably three or more components A to D mentioned above - is further characterized in that the formula for the most part, preferably substantially exclusively, contains highly available calcium ions. biological, for example as described below.

Preferably the infant formula according to the invention is in the form of a powder which, before use, should be dissolved by the end user (i.e. a parent) in warm or cold, preferably lukewarm water or another suitable liquid carrier, for example in an amount c and 9-17 g of powder per 100 ml of water. Both such a powder, optionally packaged in suitable containers such as tin cans, boxes, pouches, bottles or sachets, as well as a ready-to-eat milk formula obtained by dissolving such a powder, together constitute the essence of the present invention.

Preferably, the infant formula according to the invention contains at least one component A and / or at least one component B in the amounts indicated below, i.e. in combination with at least one, preferably at least two, most preferably all three of the other ingredients.

The components [B to D] or [A, C and / or D], respectively; and optionally contains one or more further ingredients.

More preferably, the infant formula according to the invention comprises a combination of components A + B + C, and optionally one or more further ingredients.

Generally, in a preferred embodiment, the infant formula of the invention containing at least components A and B comprises the above ingredients in the following amounts

<td colspan="4">relative values:</td>

<td>- component A:</td><td> 6,4</td><td>down</td><td>16.0% by weight</td>

<td>- component B:</td><td> 18</td><td>down</td><td>29.0% by weight</td>

<td>- component C:</td><td> 0</td><td>down</td><td>15.0% by weight</td>

<td>- component D:</td><td> 0</td><td>down</td><td>15.0% by weight</td>

<td>- further ingredients:</td><td> 0</td><td>down</td><td>60.0% by weight</td>

to a total weight of the final dairy formula (e.g. in powder form) of 100% by weight.

In a more preferred embodiment, the infant formula t of the invention comprising at least components A, B and C comprises the above components in the following relative amounts:

<td>- component A:</td><td> 6,4</td><td>down</td><td>16.0% by weight</td>

<td>- component B:</td><td> 18</td><td>down</td><td>29.0% by weight</td>

<td>- component C:</td><td> 3,0</td><td>down</td><td>15.0% by weight</td>

<td>- component D:</td><td> 0</td><td>down</td><td>15.0% by weight</td>

<td>- further ingredients:</td><td> 0</td><td>down</td><td>60.0% by weight</td>

to a total weight of the final dairy formula of 100% by weight.

In general, the infant formula of the invention containing all four components A, B, C and D contains the above components in the following relative amounts:

<td>- component: A:</td><td> 6,4</td><td>down</td><td>16.0% by weight</td>

<td>- component B:</td><td> 18</td><td>down</td><td>29.0% by weight</td>

<td>- component C:</td><td> 3,0</td><td>down</td><td>15.0% by weight</td>

<td>- component D:</td><td> 1,5</td><td>down</td><td>15.0% by weight</td>

<td>- further ingredients:</td><td> 0</td><td>down</td><td>60.0% by weight</td>

to a total weight of the final dairy formula of 100% by weight.

It has been found that several infant milk formulas according to the invention can be developed, preferably with different properties, with a certain choice of flavors, and / or for infants of different ages.

Moreover, it has been found that the milk mixtures may differ with regard to the presence of components A to D and further components; in terms of the use of individual compounds / ingredients as components A to D and / or further components; and / or in terms of the (relative) amounts of ingredients used.

Finally, it has been found that it is possible to develop the infant formula according to the invention for infants below 6 months of age, as well as the infant milk formula according to the invention for infants below 4 months of age, and in particular also above 6 months of age. This issue will be discussed in more detail below.

Proteins which are preferably used as component A have a relatively low phosphorus content. 100 g of protein must provide less than 0.75 g of phosphorus, preferably less than 0.72 g and even more preferably less than 0.69 g. Suitable sources are whey protein, dephosphated casein or soy protein and mixtures thereof, as well as specific protein fractions from caseins - such as those from which some, more preferably most, α-caseins have been removed.

Protein hydrolysates, which are preferably used as component A, form a further and separate aspect of this invention, as is the method of preparing such preferred hydrolysates. It has been found that such hydrolysates may find other uses in addition to their use in the milk formulas of the invention, as discussed below.

Preferred protein A hydrolysates - when used in the amounts indicated below - will generally provide the final formula dairy of the invention having one or more - preferably all - of the following properties:

- a peptide profile - as for proteins derived from a preferred hydrolyzate - as described below;

PL 199 368 B1

good taste, in particular a taste that is devoid of bitterness, which is a particularly important characteristic for the infant formula in general as well as for the infant formula according to the invention;

- content of free amino acids less than 10 g and preferably less than 7 g per 100 g of protein equivalent (calculated by multiplying the Kjeldahl nitrogen by 6.25; where the amount of nitrogen measured is determined from the amount of proteins, peptides, amino acids and other nitrogen sources in product), based on the final milk formula;

- an osmolarity less than 270 mOsmol / l, preferably less than 230 mOsmol / l. An osmotic value within this range will ensure, inter alia, that the formula of the invention does not interfere (e.g. inhibit) the natural gastric emptying processes of an infant;

- low sensitization, as assessed for example by the tests described by JJ Pahud and K. Swartz in "Proc. of the Tropical Conference, Virginia 1985, AOAC, 264-271; and / or Piacentini et al., in "Allergy, 1994, 48, 361-364, or by other appropriate tests.

In the tests of this type described by Pahud and Swartz or by Piacentini, the infant formula according to the invention preferably shows a degree of sensitization of substantially zero.

Moreover, in accordance with one preferred aspect, when the infant formula according to the invention comprises the preferred lipid component B described below, the formula according to the invention may have a reduced fat content above all, compared to traditional infant formulas. In accordance with this aspect of the invention, the formula according to the invention may primarily have a fat content (expressed as total lipid content) of less than 46% by weight, compared with a value of 48% by weight or more for conventional infant formulas.

In the formula of the infant formula, medium chain fatty acid triglycerides (MCTs) may be used in the infant formula to partially replace triglycerides containing palmitic acid residues. In this case, the medium chain triglycerides (MCTs) are preferably used in an amount of less than 20% by weight based on the total weight of the lipid component B.

As described below, when the infant formula according to the invention contains the preferred lipid component B, the infant formula according to the invention may also not require the amount of calcium present therein to be as high as the required calcium content in conventional milk formulas. .

In particular, according to one aspect of the invention, the formula of the invention for infants less than 6 months of age may have a calcium content (expressed as mg of calcium per 100 kcal of energy contained in the formula) of less than 80 mg / 100 kcal, preferably less than 77 mg / 100 kcal (for example 70 mg / 100 kcal); compared to 82-120 mg / 100 kcal for traditional infant formula. In order to provide the infant with sufficient calcium, the calcium concentration should be above 50 mg / 100 kcal.

The formula of the invention for infants over 6 months of age may have a calcium content (expressed as mg of calcium per 100 kcal of the energy contained in the formula) of less than 122 mg / 100 kcal, preferably less than 116 mg / 100 kcal (for example 110 mg / 100 kcal); compared to 125 mg / 100 kcal for traditional infant formula t.

Such reduced calcium content may provide certain benefits such as reduced intestinal fatty acid soap production and a more natural exposure of calcium ions to the action of erythrocytes in the duodenum and other parts of the intestine and to the action of the intestinal flora. In addition, it has been found that in this case, for example, when producing such a milk mixture, fewer technological problems related to the occurrence of sedimentation occur.

The calcium is preferably added to the infant formula according to the invention in the form of a soluble salt (s) such as the hydroxide or chloride salts. The tribasic phosphate and citrate salts are insoluble. In addition, it is also an object of the invention to prevent the formation of insoluble calcium salts such as phosphates and / or citrates during the production of the formula milk.

As in infant formula the amount of phosphorus present is essentially dependent on the amount of calcium, so that in traditional formulas the ratio of calcium to phosphorus is essentially

The ratio is between 1.5 and 2.0, and usually around 2, which is why the phosphorus content of the infant formula according to the invention may also be reduced.

For example, based on the calcium contents mentioned above and an overall calcium to phosphorus ratio of about 2, the formula of the invention for infants less than 6 months of age may have a phosphorus content (expressed as mg of phosphorus per 100 kcal of energy contained in the formula) less than 40 mg / 100 kcal and preferably less than 38.5 mg / 100 kcal (e.g. 38 mg / 100 kcal); while the formula of the invention for infants over 6 months of age may have a phosphorus content (expressed as mg of phosphorus per 100 kcal of the energy contained in the formula) of less than 61 mg / 100 kcal, preferably less than 58 mg / 100 kcal (per example 38 mg / 100 kcal).

Such a reduced phosphorus content may provide some advantages, such as less sedimentation in the preparation of such a milk formula and increased bioavailability of the divalent cations.

If, in addition to the phosphorus provided by the proteins and / or phospholipids, additional phosphorus must be added to the formula milk, this is done in particular by the addition of monobasic phosphates, preferably sodium and / or potassium.

Alternatively, where the infant formula has a reduced calcium content as described above, the formula according to the invention may be produced with a reduced calcium to phosphorus ratio in the range of 1.4 to 2. This reduced proportion of calcium to phosphorus may also provide certain benefits, such as compensating for some of the properties of the water used by the last consumer to prepare the formula, that is, by dissolving the formula of the invention in powder form.

Moreover, when one or more prebiotic C ingredients are present in the infant formula of the invention, their content is preferably at least 0.3 g / 100 ml of the total weight of the formula, more preferably at least 0.6 g / 100 ml of the total weight of the formula. milk mixture. When formula is fed to infants in conventional amounts - for example at least about 200 ml per day (this depends primarily on the infant's age) of one or more, preferably 4 or more feedings per day - this will correspond to a total daily intake of at least a prebiotic ingredient. 1.8 g / day (which again depends primarily on the age of the infant).

Moreover, when the milk formula comprises one or more viscosity improving ingredients D, the viscosity of the final milk formula is preferably in the range of 20 to 100 cps, more preferably in the range of 40 to 80 cps; when measured with a Brookfield viscometer at 30 rpm.

The infant formula according to the invention preferably has a pH in the range 4.0 to 7.5.

Moreover, in accordance with one specific embodiment of the invention, the infant formula according to the invention may (also) be low in lactose in order to prevent and / or reduce the problems associated with (partial) lactose intolerance and / or reduced lactase activity in the colon. In this embodiment of the invention, the infant formula of the invention comprises any combination of at least two, preferably at least three and most preferably all four components A to D; and it has a lactose content of at most 6.0 g / 100 ml, preferably less than 4.5 g / 100 ml, more preferably less than 3.0 g / 100 ml of the total formula weight; when it is determined by a lactose test known in the art.

Such formula may be of particular importance for infants who are lactose intolerant and / or suspected to be lactose intolerant, for example because they are immature and / or have low lactase activity, for example with due to hereditary factors.

The infant formula according to the invention can generally be prepared by mixing / combining together the various ingredients / ingredients in the amounts specified therein. This can generally be done as known in the art using well known mixing and / or processing equipment. The infant formula may also be heated / sterilized (e.g. by UHT treatment), after which it is preferably made into a powder, e.g. by evaporation or drying (spray-drying) and aseptically packaged, e.g. in suitable containers such as tin cans, boxes, bags, bottles or sachets. A preferred method of preparing the infant formula of the invention, starting from the preferred protein hydrolysates used in this invention, will be discussed in detail below.

Components A to D and further components used in the present invention will be discussed in detail below. Accordingly, it will be apparent to a person skilled in the art that any ingredients or ingredients used in the infant formula according to the invention should be approved for use in food products, and in particular should be acceptable for use in formula for infants. babies. In addition, any ingredients or ingredients used herein should preferably be compatible with the other ingredients / ingredients of the final formula, and more preferably not (too much) deviate from the desired properties of the final formula for infants, including but not limited to those properties. provided by any of the other ingredients / ingredients.

l. Component A

Component A contains intact proteins, protein hydrolyzate, or combinations thereof.

Component A is preferably such that it is low in phosphorus and preferably also such that it is easily digestible. Preferably, this protein source also provides all the amino acids needed for optimal growth in sufficient amounts. Suitable sources of component A include specific protein fragments from mammalian milk or a low phosphorus protein of vegetable origin such as soy protein. For infants who may be intolerant to intact proteins, most preferably these proteins need to be hydrolyzed.

Preferably component A is a protein hydrolyzate obtained by hydrolyzing one or more milk proteins, especially cow's milk, including but not limited to proteins, protein fragments and / or protein preparations derived from whole milk, skim milk, casein and / or whey.

In principle, any milk protein hydrolyzate known per se which is suitable for use in food products, and in particular which is suitable for use in infant formula; such hydrolysates are well known in the art.

Preferably the protein hydrolyzate used has one or more, preferably all of the features a) to e) listed below. For this reason, although it is not excluded that some methods known in the art may provide a protein hydrolyzate which has one or more of the desired characteristics a) to e) - as also such hydrolysates can be used in a milk formula for infants of the invention - it is this invention that also provides a range of preferred protein hydrolysates as well as a method of producing such preferred protein hydrolysates, which simultaneously show all of the desired features a) to e). The use of such hydrolysates is particularly preferred.

In particular, the protein hydrolyzate used in this invention should have one or more of the following characteristics:

a) the hydrolyzate should contain all the amino acids necessary for the good growth of the infant;

b) at least 50% by weight of the proteins present in this hydrolyzate (based on all protein components present in the mixture, including any free amino acids) should have a chain length in the range of 2 to 30 amino acids, preferably in the range of 2 to 15 amino acids, and most preferably in the range of 3 to 12 amino acids; the remainder are also the protein components with more amino acids in the protein chain and / or free amino acids. Preferably, these remaining protein components, representing 0.5 to 8%, preferably 0.7 to 7%, and most preferably 0.75 to 5%, will have chain lengths greater than 30 amino acids. The presence of small oligopeptides improves the digestibility of these proteins and thus the digestibility of the entire infant formula of the invention. The presence of oligopeptides ranging in length from 15 to 30 amino acids will also allow the infant's digestive system to habituate to larger and / or intact proteins.

c) low osmolarity due to the low content of free amino acids and salts. This prevents gastrointestinal disorders such as diarrhea or at least (subsequently) reduces the risk of their occurrence and prevents the stomach from emptying too slowly. In this regard, it should be noted that since the infant formula according to the invention is especially intended for infants who have problems with the adaptation of the infant formula / formula - for example, those who suffer from one or more more disorders mentioned in the introduction - it is especially important that the milk mixtures according to

According to the invention, they may be high in protein, if desired. This makes it of paramount importance to control the osmolarity of the protein hydrolyzate used to prepare the formula of the invention.

As mentioned above, a low content of free amino acids is also very important, as free amino acids can cause this hydrolyzate - and thus the whole milk mixture - to taste bitter. In order to mask such a bitter taste, it would be necessary to add sweeteners to such a milk mixture, especially sweeteners containing many free sugars such as glucose syrup and some starch hydrolysates (for example from corn or peas). These, however, have a substantially high osmolarity (such starch hydrolysates have a DE value of&gt; 35) which in turn would cause (too much) an increase in osmolarity in the final dairy formula.

Thus, it is a further aspect of the invention to provide an infant formula based on a protein hydrolyzate which may contain less sweeteners and / or low osmolarity sweeteners (for example with a DE of less than 30). Preferably, as already mentioned above, when the hydrolyzate is incorporated into the infant formula of the invention in the amounts indicated herein - the osmolarity of the protein hydrolyzate is suitably such that the osmolarity of the final formula is less than 270 mOsmol / l, preferably less than 240 mOsmol / 1, and more preferably less than 230 mOsmol / L;

d) good taste, in particular a bitterness free taste, which is a particularly important feature for (protein hydrolysates used in the preparation) of infant formula.

The taste, and in particular the bitterness, of this protein hydrolyzate can, for example, be determined in a comparative test using a flavor table and using a suitable compound such as caffeine or a standard hydrolyzate as a flavor reference.

For example, in the flavor board trial described in Example 2 of US-A-5,837,312 using a 5% solution of the test compound and using caffeine as a flavor reference, each hydrolyzate intended for use in making the infant formula of the invention preferably should have a flavor. less than 2.7 bitter; preferably less than 2.4, more preferably in the range 1.6 to 2.3 (on a scale of 1 to 6, where 6 is the value for the caffeine flavor reference).

As is known in the art, the bitter taste of protein hydrolysates is (at least in part) due to the presence of free amino acids that are formed during the hydrolysis, such as free phenylalanine and / or tyrosine. Thus, in hydrolysates intended for use in the infant formula of the invention, the amounts of such free amino acids should be as low as possible, i.e. not more than 10% by weight, preferably not more than 7% by weight, based on all ingredients. protein (including free amino acids).

e) low sensitization rate, for example as assessed by the test described by JJ Pahud and K. Swartz in "Proc. of the Tropical Conference, Virginia 1985, AOAC, 264-271; and / or Piacentini et al. in "Allergy, 1994, 48, 361-364 or by other suitable tests. Preferably, the protein hydrolyzate is such that, when the hydrolyzate is incorporated into an infant formula in the amounts indicated herein, the final milk formula according to the invention in the tests described by Pahud and Swartz or by Piacentini preferably exhibits a degree of sensitization substantially equal to zero .

As is known in the art, the allergic properties of the protein hydrolyzate - and thus the infant formula if it is included therein - are largely dependent on the types and amounts of proteins that will be formed during and which remain after hydrolysis. Therefore, the use of a protein hydrolyzate obtained as described below is particularly advantageous.

Although the imbalance in the osmolarity of the protein hydrolyzate can be corrected by ion removal using techniques known in the art, it is highly desirable that the protein hydrolysates possess all of the above-mentioned features a) to e). Such a hydrolyzate can be obtained reliably by the method described below. Preferably such a protein hydrolyzate is present in the infant formula of the invention in an amount in the range 1 to 3 g / 100 ml, preferably in the range 1.3 to 2.0 g / 100 ml and more preferably in the range 1.6 to 1.9 g / 100 ml total milk formula.

PL 199 368 B1

II. A method of preparing the preferred protein hydrolysates suitable for use as component A according to the invention, and the use of this protein hydrolyzate for the preparation of a formula milk according to the invention.

As already mentioned above, this process as well as the hydrolysates obtained by this process constitute separate aspects of the present invention.

Any protein, protein mixture or protein preparation having a phosphorus content of less than 0.75 g / 100 g protein can be used as the starting material for the hydrolysis of the invention.

Especially preferred is the use of proteins from mammalian milk, especially from cow's milk such as whey and especially acid whey; dephosphated casein; β-casein, or suitable mixtures thereof.

Preferably the protein starting material has a phosphorus content of less than 0.72 g P / 100 g of protein, more preferably less than 0.69 g P / 100 g of protein. Again, these starting materials will include whey, especially acid whey, dephosphated casein, or specific casein fractions with reduced α-casein content and / or increased β-casein content.

Optionally, the starting material can be treated to remove (residual) natural enzyme activity.

Optionally, prior to carrying out the hydrolysis process according to the invention, a suspension of yeast cells, optionally homogenized and heated and / or pretreated to disrupt their cell walls, may also be added to the starting material, for example at a rate of 1-8 g dry yeast cell weight per 100 g protein. For example, an acid whey mixture containing 4% yeast protein (added as a 10% baker's yeast slurry) may be used.

Then the starting material - as such or in a suitable form such as a solution or suspension - is treated with a combination of at least one endo- and at least one exoproteinase, this enzyme mixture being added in an amount of 0.1-5% based on on the starting material.

Endo- and exoproteinases may be used sequentially - for example in two or more separate hydrolysis steps - or simultaneously, for example as a suitable mixture in a single hydrolysis step, optionally in combination with one or more hydrolysis steps using the remaining enzymes. Preferably, the hydrolysis comprises a single hydrolysis step using a combination of all enzymes that should be used.

Preferably, an appropriate mixture of serine proteases is used as endo- and exoproteinases, including, but not limited to, a suitable enzyme mixture comprising (at least) the enzymes Alcalase® and Trypsinase® (both commercially available from Novo Nordisk). Another suitable enzyme for use in such an enzyme mixture is Flavourzyme® (also commercially available from Novo Nordisk). It is particularly preferred to use a mixture of Alcalase®, Flavourzyme® and Trypsinase® in relative amounts of about 5-10 parts Alcalase® to 3-5 parts Flavourzyme® to 1 part Trypsine® (for example in a 7.5: 4: 1 mixture ), wherein the mixture is preferably used in an amount corresponding to at least 0.1% - for example about 0.2% - of Trypsine® per 100 g of starting protein.

By using such a preferred mixture as described below, a protein hydrolyzate can be obtained which is non-sensitizing despite the presence of relatively high molecular weight peptides / proteins. The use of the reaction conditions described above allows the preparation of an infant formula devoid of bitter taste and with low osmolarity (for example as described above).

Using a mixture of endo- and exoproteinases - and in particular a preferred mixture comprising Alcalase®, Flavourzyme® and Trypsine® - the starting material is hydrolyzed at about 45-60 ° C, preferably 50 to 58 ° C, for less than 4 hours, preferably at within 1.5 to 3 hours. The pH value is kept in the range of 6.4 to 8 during the hydrolysis, preferably the pH value is kept constant, for example in the range 6.8 to 7.8.

Generally, the degree of hydrolysis is not critical. In other words, irrespective of the final degree of hydrolysis, hydrolysis of the above-mentioned starting materials with the enzyme combination under the above-mentioned conditions and for the above-specified period of time will substantially lead to a protein hydrolyzate having the desired properties for use in the infant formula of the invention. Alternatively, if necessary, one skilled in the art will be able to - based on this disclosure 12

In order to obtain the protein hydrolyzate with the desired properties, adapt the above hydrolysis reaction conditions.

It should also be noted that, essentially irrespective of the use of the above starting materials and the preferred (preferred) enzyme combination, the conditions for the hydrolysis are also not very critical depending on how the hydrolyzate is (then) processed before it is used in the infant formula. according to the invention. However, it has been found that the desirable features a) to e) of the final infant formula are best and most likely obtained when the above conditions are used in conjunction with a cooling step which will now be described herein.

The hydrolysis reaction may be terminated in any manner, however, in order to provide the combination of the desired characteristics a) to e) in the final hydrolyzate, it is most preferred that the hydrolysis reaction is not terminated / quenched by heating (as usual), but instead by cooling the reaction mixture. , without specifically removing or denaturing the enzymatic activities present in this mixture.

Preferably, in the process according to the invention, the entire reaction mixture is cooled down within one hour from the hydrolysis temperature - for example from a temperature of about 45-60 ° C, preferably in the range 50 to 58 ° C - to a temperature below 20 ° C, preferably below 10 ° C. C. Such cooling preferably begins 1.5 to 3 hours after the start of the hydrolysis reaction.

Thus, an appropriate temperature protocol for hydrolysis can be as follows:

- hydrolysis (45-60 ° C, preferably 50-58 ° C) 1.5 to 4 hours.

- cooling (down to &lt;20 ° C, preferably &lt;10 ° C) 10 min to 1 hour.

- total time: 1.7 to 4.5 hours

the preferred temperature protocol for hydrolysis is as follows:

- hydrolysis (45-60 ° C, preferably 50-58 ° C) 2.0 to 3 hours.

- cooling (down to &lt;20 ° C, preferably &lt;10 ° C) 10 min to 1 hour.

- total time: 2.2 to 3.5 hours

The chilled protein hydrolyzate thus obtained may then be used as such in the preparation of the infant formula of the invention, or after appropriate treatment such as removal of one or more undesirable compounds or ingredients, including, but not limited to, salts, amino acids, and enzymes used in hydrolysis.

A treatment of this type can be carried out, for example, by desalting (for example by dialysis); by precipitation, for example acidification with a food grade acid such as hydrochloric acid to a pH &lt;5.0, followed by removal of the precipitate (e.g. by centrifugation) and re-adjustment of the pH to a suitable value, e.g. 7; or by any other suitable technique.

Instead of the entire protein hydrolyzate, only a fraction thereof may also be used, obtained for example by removing (parts of) proteins with a chain length of more than 30 amino acids.

The protein hydrolyzate thus obtained is then incorporated into the infant formula of the invention, for example by a non-limiting processing step which is preferably carried out within 24 hours, more preferably within 8 hours after the end of the hydrolysis reaction:

a) All further components of the final dairy formula are added to the protein hydrolyzate - for example lipid component (s) B; Prebiotic C component (s) (if used); optionally a portion of viscosity improving ingredient (s) D (if used); and optionally further ingredients such as vitamins, minerals and trace elements.

The mixture is then homogenized and heated to obtain the desired microbiological quality of the product without (too much) deviating from the desired characteristics of the formula and / or the desired biological activity of the ingredients included in its formulation. For example, an UHT treatment at 140 ° C for about 2.4 seconds can be applied. The product is then brought into pulverulent form - for example by evaporation and drying (spray drying). It is preferred that some of the ingredients, such as viscosity improving component D, if present, are added in powder form after the spray-drying step. The final composition can then be aseptically packaged, for example in suitable containers such as tin cans, boxes, pouches, bottles or sachets.

b) Alternatively, after adding the water-soluble ingredients to be included in the final dairy formula - such as vitamins, minerals and trace elements - the protein hydrolyzate can be heated and partially dried / evaporated, after which the ingredient (s) are added

Lipid B and further components. The mixture can then be homogenized and made into a powder. Following the optional addition of further powdered ingredients such as viscosity improvers, the final composition is packaged, for example as described above.

The infant formula produced in this way - that is, by the process described above, starting from the preferred protein hydrolyzate - has optimal characteristics (characteristics) in terms of taste, low osmolarity, low free amino acid content, reduced sensitization, and has a protein / amino acid content. one that is substantially sufficient for an infant formula.

In the above-described process according to the invention, the protein hydrolyzate is subjected to only minimal heat treatment, which ensures that the biological activity of the ingredients present in the milk formula is maintained, or at least not significantly affected.

Moreover, the above-described method reliably leads to a protein hydrolyzate and / or infant formula with the desired characteristics, which is produced safely and cost-effectively (limited use of expensive enzymes such as Trypsin® and low production costs).

Thus, in a further aspect, the present invention relates to a protein hydrolyzate obtained by the method described in Section II of the present description, an infant formula containing such a protein hydrolyzate; and the use of such a protein hydrolyzate in the preparation of an infant formula, and in particular its use as component A for the production of the infant formula according to the invention.

As already mentioned, the preferred protein hydrolyzate is present in the infant formula of the invention preferably in an amount in the range 1 to 3 g / 100 ml, more preferably in the range 1.3 to 2.0 g / 100 ml and most preferably in the range 1. 6 to 1.9 g / 100 ml total milk formula.

However, it has been found that in addition to their use in the present invention, both the method described in Section II - and the protein hydrolysates thus obtained - may find other uses, particularly in the field of food products, and particularly in the field of infant food and / or dietary food. for example for the prevention or treatment of food allergies, and for the production of food, which is designed to pass immediately through the stomach and is easily digestible. The latter products can be of great benefit to patients suffering from impaired stomach function, impaired liver function, impaired pancreatic function and / or impaired bowel function.

Thus, as mentioned above, the method described in Section II as well as the protein hydrolysates obtained by this process constitute independent and separate aspects of the invention.

III. Component B

The at least one lipid component B, for example one or more fatty components and / or fatty acids present in the infant formula of the invention, may be selected from all fatty acid triglycerides known per se for use in food products, and are preferably selected from fatty acid triglycerides and / or phospholipids (and / or mixtures thereof) known per se for use in baby food, especially among those known per se for use in infant formula.

As is known in the art, such fatty acid triglycerides generally contain a glyceride molecule to which three fatty acid residues, which may be the same or different, are attached via an ester linkage, and which are generally selected from saturated and unsaturated fatty acids containing 6 to 26 carbon atoms, including but not limited to linoleic acid, α-linolenic acid, oleic acid, palmitic acid (C₁₆) and / or stearic acid (C18).

Such fatty acid triglycerides may differ in the fatty acid residues that are present and / or the corresponding positions (position) of these fatty acid residues (for example at position 1, position 2 and / or position 3). Typically, as is known in the art, the lipid component for use in infant formula will contain a suitable mixture of two or more, usually several, different fatty acid triglycerides, depending, for example, on the desired properties of the lipid component, the source of the fat, as well as on how to obtain this fat.

Such at least one lipid component B - i.e. one or more fatty acid triglycerides as present therein - is preferably chosen such that lipid component B is lightly 14

The formula is digestible by the infant, thus making (also) the final formula easily digestible.

This improves the stool structure and improves the bioavailability of the divalent cations and / or fats / fatty acids present in the infant formula.

For this reason, the number and position of palmitic acid residues which are present in these triglycerides, which in turn constitute at least one lipid component B, are of particular importance. Preferably palmitic acid residues should constitute more than 10%, preferably 16-24% of all fatty acid residues present in these triglycerides used as or in lipid component B.

Also the amount of triglycerides in which the C14: 0, C16: 0 and / or C18: 0 fatty acids are in the Sn1 position or in the Sn3 position of glycerol, and in particular in which the palmitate residues are in the Sn1 or Sn3 position, should be be as small as possible. The amount of palmitic acid at the Sn1 position or the Sn3 position should preferably be no more than 16%, more preferably no more than 13%, and most preferably no more than 10.7% of all triglycerides present. This corresponds to an amount of triglycerides with a palmitate residue in the Sn1 or Sn2 position which is less than 0.55 g / 100 ml, preferably less than 0.50 g / 100 ml and most preferably less than 0.38 g / 100 ml of the final dairy formula. for babies.

In other words - somewhat less restrictive - when palmitic acid residues make up more than 10%, preferably 16-24% of all fatty acid residues present in these triglycerides used in or as the lipid component B of the invention, then those palmitic acid residues in the amount as much as possible, preferably at least 30%, more preferably at least 40%, should be in the 2 or β position of said triglyceride.

A mixture of fatty acid triglycerides containing more than 10%, preferably 1624% palmitate residues, which meets one or both of the palmitate positioning requirements set out in the two paragraphs above, will also be considered herein as the "preferred lipid component B." This includes, for example, specific phospholipids as well as so-called structural fats, for example fats of animal or vegetable origin, in which the triglycerides have been enzymatically or otherwise re-esterified such that the palmitic acid residues are mostly in position 2.

Such preferred B-lipid components are commercially available, for example from Loders Croklaan under the trade name Betapol® (beta palmitate), and / or may be obtained in a manner known per se, for example as described in European patents EP 0 698 078 and / or EP 0 758 846.

However, due to better absorption of such fat mixtures from the intestines of the infant, by using the above-described preferred lipid component B, it is possible to reduce the amount of component B added to the formula of the invention while still providing the infant with sufficient energy and nutritional value.

By using the preferred lipid component B, especially the total fat content of the infant formula according to the invention can be reduced from a value of 48% or higher for conventional infant formulas to values ​​less than 46% for the infant formula according to the invention.

The use of the preferred lipid component B may also allow the total calcium content of the infant formula of the invention to be lowered, i.e. as already discussed above. Such a reduction in the calcium content may in turn allow the total phosphorus content of the infant formula of the invention to be lowered, as already discussed above.

Alternatively, the use of the preferred lipid component B may allow the calcium to phosphorus ratio in the infant formula of the invention to be lowered, for example from about 2 for conventional formulas to values ​​in the range 2.0 to 1.4.

Although lipid component B has been described above as containing essentially only fatty acid triglycerides, it should be understood that the presence of smaller amounts of mono- or diglycerides is not excluded (for example, up to a total content of at most one third of all fatty acids of all mono-fatty acids). , di- and triglycerides of fatty acids present in or as component B, with the remainder being fatty acid triglycerides based on a total weight of component B of 100%). Such mono- or diglycerides will usually contain the same fatty acid residues as mentioned above.

PL 199 368 B1

IV. Component C

The one or more prebiotic ingredients C may be selected from all the prebiotic ingredients known per se for use in food products, and preferably they are selected from prebiotic ingredients known per se for use in infant food, especially those known per se for use in infant formula.

Several preferred but non-limiting examples of such ingredients include prebiotic (indigestible) oligosaccharides. Generally they will be hydrolyzed and non-hydrolyzed hydrocarbons containing sugar moieties interconnected by beta 1-1, 1-2, 1-3, 1-4, 1-6 and / or alpha 1-6 linkages. More preferably such oligosaccharides will have 2-20 sugar residues on the saccharide backbone (backbone).

Such prebiotic oligosaccharides, for example, include, but are not limited to, lacto-N-tetraose, lacto-N-fucopentaose, lactulose, lactosaccharose, raffinose, galacto-oligosaccharides, fructo-oligosaccharides, polysaccharide-based oligosaccharides, polysaccharide-derived oligosaccharides, polysaccharides-derived oligosaccharides . , arabinoligosaccharides, xylo-oligosaccharides, isomaltosaccharides, glucans, sialyl oligosaccharides and fuco-oligosaccharides, and / or suitable mixtures thereof.

Lactose can also be used as a prebiotic component. However, the use of lactose in the infant formula of the invention should be avoided when a low-lactose infant formula is desired, for example for infants who are or are suspected to be lactose intolerant (eg due to age or hereditary factors). ).

Particularly preferred is the use of one or more trans-galacto-oligosaccharides ("TOS), one or more fructo-oligasaccharides (" FOS), and / or mixtures thereof, and especially the use of mixtures of one or more trans-galacto- oligosaccharides and one or more fructo-fructosaccharides. - oligosaccharides in which the ratio of TOS to FOS is in the range of 5: 1 to 15: 1, in particular about 9: 1, which mixtures generally provide a prebiotic effect comparable to that of mother's milk.

In general, the amounts of one or more prebiotic components C used will depend on the specific component (s) C used, as well as the amount of formula that will be given to the infant per day, for example one or more, preferably four or more feeds per day. In general, the amounts of the prebiotic component (s) C used will be such that - when the formula is administered to an infant in the recommended / prescribed amounts - it will be sufficient to administer a daily dose of the prebiotic component (s) of at least 1.8 g / day for infants in age less than 4 months; and preferably in an amount of at least 3.6 g / day for infants older than 4 months. Typically the infant will be fed with a total weight in the range 550 to 800 ml of formula according to the invention per day. Thus, the above amounts correspond to an amount of prebiotic component (s) C of at least 0.3 g / 100 ml total formula formula, more preferably at least 0.6 g / 100 ml total formula formula.

The use of the above prebiotic substances in the infant formula of the invention may (help) preserve the natural flora of the gastrointestinal tract and / or reduce the presence of aggressive ingredients in the stool, for example ingredients that can irritate or damage epidermal cells ( such as those lining the gastrointestinal tract and / or leather). The latter feature is especially important for babies suffering from diaper rash.

V. Component D

The one or more viscosity improving ingredients D may be selected from all viscosity improving ingredients known per se for use in food products, and are preferably selected from viscosity improving ingredients known per se for use in infant food, in particular those known per se. for use in infant formula; see, for example, the disclosure of European Patent EP 0 846 422.

Several preferred but non-limiting examples of such ingredients include carbohydrate based viscosity enhancing ingredients, especially those based on starch and / or starch derivatives such as pregelatinized starches such as pregelatinized potato starch, which is the preferred material.

PL 199 368 B1

In general, the amounts of one or more viscosity-improving ingredients D used will depend on the specific viscosity-improving ingredient (s) used and on the other ingredients present in the formula concerned, and will generally be such that the viscosity of the final formula is in the range of 20 to 100 cps. preferably in the range of 40 to 80 cps when measured in a Brookfield viscometer at 30 rpm. Typically the total amount of viscosity improving component (s) D will be in the range of 0.5 to 5 g / 100 ml of the formula, preferably in the range of 1 to 3 g / 100 ml. For example, pregelatinized potato starch may be used in an amount in the range of 1.4 to 2.1 g / 100 ml.

The use of viscosity-improving component (s) D can provide several benefits, including, but not limited to, prevention or reduction of regurgitation and / or excessive glaucoma (belching).

VI. Further ingredients

In addition to the aforementioned components A to D, the composition of the invention may further comprise any component or ingredient known per se for infant formula, in the usual amounts (for example as prescribed in national or international standards) depending on the desired final formula . . Such further ingredients may include, but are not limited to, one or more of the following combinations:

- one or more of the following compounds: taurine, choline, camitin, inositol, biotin;

- one or more of the following polyunsaturated chain fatty acids ("PUFAs), including but not limited to linoleic acid, α-linolenic acid, oleic acid, arachidonic acid and docosahecasanoic acid;

- one or more nucleotides and / or nucleotide analogues;

- one or more (additional) amino acids, including but not limited to tryptophan and / or methionine;

- one or more (additional) vitamins, including but not limited to vitamin K, vitamin B1, vitamin B2, vitamin A, vitamin E, vitamin D, vitamin C, niacin, pantothenic acid. In addition to the usual amounts of these or other vitamins, the infant formula according to the invention may also contain additional amounts of - for example - folic acid, vitamin B12 and / or vitamin B6;

- one or more minerals and / or trace elements;

- one or more preservatives (not recommended);

- one or more flavoring and / or coloring agents.

Examples

Example 1: Milk formula for infants over 4 months of age

Formula for infants over 4 months of age is generally prepared as described in Section II above. This formula has the following composition, with an energy content / nutritional value of 72 kcal / ml and an osmolarity of 260 mOsmol / l. The calcium content is 86 mg / 100 kcal and the phosphorus content is 54 mg / 100 kcal.

<td>Ingredient:</td><td colspan="2">g per 100 g of powder g per 100 ml *</td>

<td>Protein Equivalents:</td><td> 12,4</td><td> 1,9</td>

<td>whey protein hydrolyzate **</td><td></td><td> 1,9</td>

<td>Carbohydrates:</td><td> 54,8</td><td> 8,6</td>

<td>saccharides (lactose)</td><td></td><td> 4,0 (2,7)</td>

<td>maltodextrin polysaccharides</td><td></td><td> 2,0</td>

<td>potato starch polysaccharides</td><td></td><td> 2,3</td>

<td>organic acids</td><td></td><td> 0,1</td>

<td>Fats:</td><td> 21,1</td><td>3.3 (= 41 wt.%)</td>

<td>saturated</td><td></td><td> 1,4</td>

<td>beta palmitate (Loders Croklaan)</td><td></td><td> 0,23</td>

<td>mono-unsaturated</td><td></td><td> 1,4</td>

<td>multi-unsaturated</td><td></td><td> 0,54</td>

<td>Fiber / indigestible oligosaccharides:</td><td> 5,0</td><td> 0,78</td>

<td>TOS</td><td></td><td> 0,7</td>

<td>FOS</td><td></td><td> 0,08</td>

Further ingredients:

PL 199 368 B1 minerals, trace elements and vitamins in amounts prescribed by Rule 321 EEC Notes:

*: obtained by dissolving 15.6 g of powder in 100 ml of water **: preferred protein A hydrolyzate as described in Section II above

Example 2: Milk formula for infants under 6 months of age

Formula for infants less than 6 months of age is generally prepared as described in Section II above. This formula has the following composition, with an energy content / nutritional value of 70 kcal / ml and an osmolarity of 240 mOsmol / l. The calcium content is 53 mg / 100 kcal and the phosphorus content is 27 mg / 100 kcal.

Ingredient: g per 100 g of powder g per 100 ml *

<td>Protein Equivalents:</td><td> 11,6</td><td> 1,7</td>

<td>whey protein hydrolyzate **</td><td></td><td> 1,7</td>

<td>Carbohydrates:</td><td> 55,4</td><td> 8,3</td>

<td>saccharides (lactose)</td><td></td><td> 4,0 (2,9)</td>

<td>maltodextrin polysaccharides</td><td></td><td> 1,5</td>

<td>potato starch polysaccharides</td><td></td><td> 1,8</td>

<td>Fats:</td><td> 21,1</td><td>3.3 (= 42 wt.%)</td>

<td>saturated</td><td></td><td> 1,4</td>

<td>beta palmitate</td><td></td><td> 0,23</td>

<td>mono-unsaturated</td><td></td><td> 1,4</td>

<td>multi-unsaturated</td><td></td><td> 0,54</td>

<td>Fiber / indigestible oligosaccharides:</td><td> 5,0</td><td> 0,78</td>

<td>TOS</td><td></td><td> 0,7</td>

<td>FOS</td><td></td><td> 0,08</td>

Further ingredients:

minerals, trace elements and vitamins in the amounts recommended by Rule 321 EEC Notes:

*: obtained by dissolving 15.0 g of powder in 100 ml of water **: preferred protein A hydrolyzate as described in Section II above

Example 3: Milk formula for infants under 4 months of age

Formula for infants less than 4 months of age is generally prepared as described in Section II above. This formula has the following composition, with an energy content / nutritional value of 67 kcal / ml and an osmolarity of 230 mOsmol / l.

The calcium content is 45 mg / 100 kcal and the phosphorus content is 25 mg / 100 kcal.

<td colspan="4">Ingredient: g per 100 g of powder g per 100 ml *</td>

<td>Protein equivalents: whey protein hydrolyzate **</td><td> 10,5</td><td> 1,54</td><td> 1,46</td>

<td>from L-tryptophan</td><td></td><td></td><td> 0,01</td>

<td>from L-methionine</td><td></td><td></td><td> 0,01</td>

<td>from hydrolysed baker's yeast ** Carbohydrates:</td><td> 55,4</td><td> 8,3</td><td> 0,06</td>

<td>saccharides (lactose)</td><td></td><td></td><td> 3,5</td>

<td>maltodextrin polysaccharides</td><td></td><td></td><td> 3,3</td>

<td>potato starch polysaccharides</td><td></td><td></td><td> 1,8</td>

<td>Fats:</td><td> 19,2</td><td> 3,0 (=</td><td>40 wt.%)</td>

<td>saturated</td><td></td><td></td><td> 1,2</td>

<td>beta palmitate</td><td></td><td></td><td> 0,23</td>

<td>mono-unsaturated</td><td></td><td></td><td> 1,3</td>

<td>multi-unsaturated</td><td></td><td></td><td> 0,5</td>

<td>Fiber / indigestible oligosaccharides: TOS</td><td> 3,2</td><td> 0,5</td><td> 0,37</td>

<td>FOS</td><td></td><td></td><td> 0,03</td>

<td>lacto-N-tetraose Further ingredients:</td><td></td><td></td><td> 0,10</td>

<td>folic acid ^ g) vitamin K ^ g)</td><td></td><td> 10</td><td> 20</td>

PL 199 368 B1 minerals, trace elements and vitamins in amounts prescribed by Rule 321 EEC Notes:

*: obtained by dissolving 15.0 g of powder in 100 ml of water **: preferred protein A hydrolyzate as described in Section II above

Example 4: Milk formula for infants under 4 months of age

Formula for infants less than 4 months of age is generally prepared as described in Section II above. This formula has the following composition, with an energy content / nutritional value of 68 kcal / ml and an osmolarity of 260 mOsmol / l. The calcium content is 40 mg / 100 kcal and the phosphorus content is 20 mg / 100 kcal.

<td>Ingredient:</td><td>g per 100 ml *</td>

<td>Protein Equivalents:</td><td> 1,30</td>

<td>hydrolyzed β-casein / whey (40/60)</td><td> 1,29</td>

<td>from L-tryptophan</td><td> 0,01</td>

<td>Carbohydrates:</td><td> 8,5</td>

<td>lactose</td><td> 5,5</td>

<td>polysaccharides</td><td> 2,8</td>

<td>Lipids:</td><td> 3,2</td>

<td>saturated</td><td> 1,5</td>

<td>with β-palmitate</td><td> 0,2</td>

<td>with MCTs + coconut oil</td><td> 1,1</td>

<td>mono-unsaturated</td><td> 1,2</td>

<td>multi-unsaturated</td><td> 0,5</td>

<td>Fiber / indigestible oligosaccharides:</td><td> 0,5</td>

<td>arabinosaccharides</td><td> 0,4</td>

<td>FOS</td><td> 0,1</td>

<td>lacto-N-tetraose</td><td> 0,10</td>

Further ingredients:

minerals, trace elements and vitamins in the amounts recommended by Rule 321 EEC

Comments:

*: obtained by dissolving 14.5 g of powder in 100 ml of water

Example 5: Comparative Study

The effects of the formula of Example 2 were tested on 51 term infants and compared with those of a standard commercially available product containing no beta palmitate and an unadjusted calcium to phosphorus ratio. After longer feeding with these milk formulas, significantly fewer problems with constipation (p &lt;0.05), abdominal discomfort (p &lt;0.005) and less gastrointestinal problems (p &lt;0, 01) as well as fewer problems related to discomfort in the digestive tract ( cramps and crying) compared to standard formula milk.